Abstract
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD.
Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I–II/A–B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography–high resolution mass spectrometry metabolomics platform.
Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10−7). Sex stratification indicated that the separation was driven by females (p=2.4×10−7) relative to males (p=4.0×10−4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10−3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p<0.0001), but not females (r=0.44; p=0.15), potentially related to observed dysregulation of the miR-29 family in the lung.
These findings highlight the role of oxidative stress in COPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin–lysoPA axis, are associated with disease mechanisms and/or prevalence.
Abstract
Oxidative stress and the autotaxin–lysoPA axis evidence sex-associated metabotypes in the serum of COPD patients http://ow.ly/kAeE309MpdI
Footnotes
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Support statement: This study was funded by the Swedish Heart-Lung Foundation (HLF 20140469, HLF20130486 and HLF20100463), the Swedish Research Council (2016-02798, K2014-58X-22502-01-5 and K2014-58X-22502-01-5), the Swedish Foundation for Strategic Research (SSF), VINNOVA (VINN-MER), EU FP6 Marie Curie, Karolinska Institutet, AFA Insurance, the King Oscar II Jubilee Foundation, the King Gustaf V and Queen Victoria's Freemasons Foundation, the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, and the Karolinska Institutet and AstraZeneca Joint Research Program in Translational Science (ChAMP; Centre for Allergy Research Highlights Asthma Markers of Phenotype). S.N. Reinke was supported by a Canadian Institutes of Health Research Fellowship (MFE-135481). C.E. Wheelock was supported by the Swedish Heart Lung Foundation (HLF 20150640). Å.M. Wheelock was supported by the Swedish Heart-Lung Foundation (HLF20120801 and HLF20160427). Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com
- Received November 25, 2016.
- Accepted March 2, 2017.
- Copyright ©ERS 2017
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